Human papillomaviruses (HPV) are common sexually transmitted agents throughout the world. The causal association between HPV and anogenital cancer is generally accepted. What has not been well studied is the role of HPV as a risk factor for the acquisition of HIV. Sexually transmitted diseases (STDs) such as gonorrhea and chancroid have been shown to be cofactors for HIV acquisition. Very little information is available regarding the role of HPV infection and anal intraepithelial neoplasia (AIN) or cervical intraepithelial neoplasia (CIN) in facilitating HIV infection. HPV- associated AIN and CIN can enhance susceptibility to HIV infection because of increased microvasculature and bleeding. These lesions are also rich in CD4+ lymphocytes and dendritic cells that are mucosal targets of HIV infection. The specific aims of this study are to: 1) examine the role of AIN and CIN as cofactors for HIV acquisition, 2) examine the association of HPV infection with HIV acquisition, and its role in predicting AIN and CIN, and 3) identify specific bioimmunologic markers of AIN or CIN that predict HIV acquisition. A primary aim of this research is to support the career development of the applicant who is pursuing a career in patient-oriented research through the combination of direct mentoring, supervised study and clinical activities at the General Clinical Research Center and the AIDS Research Institute. The proposed research plan is a case-control study of 140 incident HIV cases that will be identified over 4 years from the ongoing Options Project, an NIAID-funded study of women and men with primary HIV infection (PHI). The referent group will be 140 men and women referred to the Options Project because of possible PHI but found to be HIV -negative. All participants will undergo anal HPV testing, high-resolution anoscopy (HRA) and anal cytology. Women will also undergo the same procedures as well as cervical PAP smears and colposcopy. To control for potential confounding, self reports regarding sexual behavior, drug use, STD history and laboratory data for STDs will be collected and included in statistical models of the effects of HPV-associated findings on HIV acquisition. The proposed research is the first to use HRA and cervical colposcopy to examine AIN and CIN as independent risk factors for HIV transmission. If HPV-associated epithelial abnormalities are risk factors for HIV infection, then identification of such lesions may improve assessment of HIV transmission risk and could direct future interventions for HIV prevention. [unreadable] [unreadable]